SVC112 is a translation elongation inhibitor that obstructs the periodic dissociation of EF2 from the ribosome, thereby inhibiting the elongation phase of translation. It demonstrates inhibitory activity in multiple cancer cell lines, including acute myeloid leukemia (AML), multiple myeloma, colorectal cancer (CRC), and head and neck squamous cell carcinoma (HNSCC). SVC112 preferentially impedes ribosomal processing of mRNA, reducing cancer stem cell (CSC)-related proteins such as Myc and Sox2. In hematological cancer cell lines, it induces apoptosis, whereas in colorectal cancer lines, the phosphorylation of c-Myc correlates with sensitivity to SVC112. The compound effectively inactivates HNSCC stem cells in vitro and prevents tumor regrowth in mouse HNSCC xenograft models. SVC112 is applicable for research on head and neck squamous cell carcinoma.

SVC112 is a chemical compound that, over a concentration range of 0-10 μM for 72 hours, exhibits broad-spectrum growth inhibitory effects on various cancer cell lines. For acute myeloid leukemia (AML), it shows activity in BDL-1, MV-4-11, HL-60, and MOLM-13 cells with IC50 values below 0.1 μM, and in THP-1, NOMO-1, MONO-MAC-6, and U-937 cells with IC50 values of 0.1-0.5 μM, while Kasumi-3 and KG-1a cells show an IC50 greater than 1 μM. In multiple myeloma, it affects NCI-H929, L-363, RPMI-8226, OPM-2, U266, MM.15, and MM.1R cells with IC50 values below 0.1 μM, and LP-1 cells with IC50 values of 0.1-0.5 μM. For colorectal cancer, SVC112 demonstrates an IC50 below 0.1 μM in SW48, RKO, HCT116, WiDr, and CL-34 cells, an IC50 of 0.1-0.5 μM in HT29, MDST8, COLO201, GP2D, NCI-H747, SNU70, SW837, and SW403 cells, and an IC50 greater than 1 μM in DLD-1, T84, KM-12C, SW948, Q-11, HCT-15, and SW48 cells. It also shows an IC50 below 0.1 μM in FaDu cells for head and neck squamous cell carcinoma. At 1 μM concentration for 2 hours, SVC112 inhibits new protein synthesis in MV-4-11, NCI-H929, HCT116, FaDu, DLD-1, and SW948 cells, while at 1 μM for 6-24 hours, it induces apoptosis in AML and myeloma cell lines (AML-EOL-1, MV-4-11, OCI-AML-3, NCI-H929, RPMI-8226, and U226B1 cells) but not in colorectal or head and neck squamous carcinoma cell lines (HCT116 and FaDu cells). At 1 μM for 6 hours, SVC112 displays differential sensitivity in colorectal cancer cell lines (DLD-1 and SW948) associated with c-Myc status. Combining SVC112 (0.2-0.4 μM) with Ulixertinib (1 μM) enhances growth inhibition. SVC112 (5-1000 nM, 2 h) inhibits protein synthesis and proliferation in Det562 and FaDu head and neck cancer cells, amplifying the effects of radiotherapy. It inhibits cap-independent translation of luciferase mRNA in vitro in rabbit reticulocyte lysates with an IC50 of 81 nM and shows antiproliferative effects in 036C, 067C, 049C, and 013C cells with IC50 values of 3.8 nM, 9.3 nM, 24.1 nM, and 50.5 nM, respectively. Over 10 days, SVC112 (10-1000 nM) reduces spheroid formation in 013C, 036C, 049C, and 067C squamous carcinoma cells. SVC112 (100 nM, 0-24 h) depletes proteins by affecting translation rather than transcription and more effectively inhibits translation in head and neck squamous carcinoma cells (013C, 036C, 049C, 067C) compared to autologous non-cancer cells. It leads to reversible protein depletion and a lasting impact on cancer stem cell properties at concentrations of 100-1000 nM for 6-48 hours. Furthermore, SVC112 induces anti-spheroid formation effects in 013C, 036C, 067C, and 049C cells at 100-1000 nM for 24 hours, which can be rescued by exogenous Sox2 expression. Lastly, SVC112 enhances the efficacy of radiotherapy in 013C, 036C, 067C, and 049C cells by delaying DNA repair when administered at 100 nM for 12-24 hours.

SVC112, administered at 60 mg/kg through intraperitoneal injection once daily for three weeks, demonstrates efficacy in mouse xenograft models of MV-4-11, AML-EOL-1, and HCT116 cells. When combined with Ulixertinib, SVC112 at 15 mg/kg via intraperitoneal injection once daily for three weeks, inhibits tumor growth in the DLD1 mouse xenograft model. Additionally, SVC112, at a dose of 60 mg/kg administered four times weekly for 28 days, shows significant tumor growth inhibition as a monotherapy or in combination with radiotherapy in CUHN036, CUHN047, CUHN004, and CUHN013 PDX models.